The proposed experiments are designed to elucidate mechanisms which operate to control levels of ribonucleic acid synthesis in mammalian cells. Infection of appropriate cells with picornaviruses results in rapid inhibition of cellular ribonucleic acid synthesis. This effect is mediated primarily through inhibition of the initiation step in RNA synthesis catalyzed by RNA polymerase II. This step involves an interaction between the enzyme and a chromatin template. Therefore, both of these cellular components will be analyzed systematically to determine the molecular basis of the inhibition. The analysis will include determinations of RNA polymerase structure, chromatin template activities, nuclear protein modifications, etc., in cells infected with picornaviruses. BIBLIOGRAPHIC REFERENCES: Linsley, S.W., Penhoet, E.E., and Linn, S.M. Human Endonuclease Specific for Apurinic/Apyrimidinic Sites in DNA. J. Biol. Chem. 252, 1235-1242 (1977). Privalsky, M. and Penhoet, E.E. A Phosphorylated Protein Component Present in Influenza Virions. J. Virol., in press 1977.